The Evaluation of Subclinical Hypothyroidism in Children with Morbid Obesity

Authors: Mustafa M. Donma, Orkide Donma

Abstract:

Cardiovascular (CV) pathology is one of the expected consequences of excessive fat gain. The role of zinc (Zn) in thyroid hormone metabolism (THM) is a matter of debate. Both thyroid stimulating hormone (TSH) and Zn levels are subject to variation in obese individuals. Zn participates in THM. It is closely related to TSH. Since thyroid hormones are required for Zn absorption, hypothyroidism can lead to Zn deficiency and vice versa. Zn exhibits protective effects on CV health and it is inversely correlated with CV markers in childhood obesity. The association between subclinical hypothyroidism (SCHT) and metabolic disorders is under investigation due to its clinical importance. SCHT is defined as the elevated serum TSH levels in the presence of normal free thyroxin (T4) concentrations. The aim of this study is to evaluate the associations between TSH levels and Zn concentrations in SCHT cases detected in morbid obese (MO) children with and without metabolic syndrome (MetS) [(MOMetS+ and MOMetS-)], respectively. 42 children were present in each study group. Informed consent forms were obtained. Tekrdag Namik Kemal University Faculty of Medicine Non-Interventional Clinical Investigations Ethical Committee approved the study protocol. World Health Organization criteria were used for obesity classification. Children with age and sex-dependent body mass index percentile values above 99 were defined as MO. Children exhibiting at least two of MetS criteria were included in MOMetS+ group. Elevated fasting blood glucose, elevated triglycerides (TRG)/decreased high density lipoprotein-cholesterol (HDL-C) concentrations, elevated blood pressure values in addition to central obesity were listed as MetS criteria. Anthropometric measures were recorded. Routine biochemical analyses were performed. In MOMetS- group 13, in MOMetS+ group 15 children were with SCHT. Statistical analyses were performed. p < 0.05 was accepted as statistically significant. In MOMetS- and MOMetS+ groups, TSH levels were 4.1 ± 2.9 mU/L and 4.6 ± 3.1 mU/L, respectively. Corresponding values for SCHT cases were 7.3 ± 3.1 mU/L and 8.0 ± 2.7 mU/L. Free T4 levels were within normal limits. Zn concentrations were negatively correlated with TSH levels in both groups. Significant negative correlation calculated in MOMetS+ group (r = -0.909; p < 0.001) was much stronger than that found in MOMetS- group (r = -0.706; p < 0.05). This strong correlation (r = -0.909; p < 0.001) calculated for cases with SCHT in MOMetS+ group was much lower in the same group (r = -0.793; p < 0.001) when all cases were considered. In conclusion, the presence of strong correlations between TSH and Zn in SCHT in both MOMetS- and MOMetS+ groups have pointed out that MO children were under the threat of CV pathologies. The detection of the much stronger correlation in MOMetS+ group in comparison with the correlation found in MOMetS- group was the indicator of greater CV risk due to the presence of MetS. In MOMetS+ group, correlation in SCHT cases found higher than correlation calculated for all cases confirmed much higher CV risk due to the contribution of SCHT.

Keywords: Cardiovascular risk, child morbid obesity, subclinical hypothyroidism, zinc.

References:

[1] R. Mullur, Y. Y. Liu, and G. A. Brent, “Thyroid hormone regulation of metabolism,” Physiol. Rev., vol. 94, no. 2, pp. 355-382, Apr. 2014.
[2] J. B. Beserra, J. B. S. Morais, J. S. Severo, K. J. C. Cruz, A. R. S. de Oliveira, G. S. Henriques, and D. do Nascimento Marreiro, “Relation between zinc and thyroid hormones in humans: a systematic review,” Biol. Trace Elem. Res., vol. 199, no. 11, pp. 4092-4100, Nov. 2021.
[3] J. S. Severo, J. B. S Morais, T. E. C. de Freitas, A. L. P. Andrade, M. M. Feitosa, L. C. Fontenelle, A. R. S. de Oliveira, K. J. C. Cruz, and D. do Nascimento Marreiro, “The role of zinc in thyroid hormones metabolism,” Int. J. Vitam. Nutr. Res., vol. 89, no. 1-2, pp. 80-88, Jul. 2019.
[4] A. Solanki, S. Bansal, S. Jindal, V. Saxena, and U. S. Shukla, “Relationship of serum thyroid stimulating hormone with body mass index in healthy adults,” Indian J. Endocrinol. Metab., vol. 17, suppl. 1, pp. 167-169, Oct. 2013.
[5] R. Xu, F. Huang, S. Zhang, Y. Lv, and Q. Liu,“Thyroid function, body mass index, and metabolic risk markers in euthyroid adults: a cohort study,” BMC Endocr. Disord., vol. 19, no. 1, pp. 58, Jun. 2019.
[6] A. Nyrnes, R. Jorde, and J. Sundsfjord, “Serum TSH is positively associated with BMI,” Int. J. Obes. (Lond)., vol. 30, no. 1, pp. 100-105, Jan. 2006.
[7] Y. Wang, X. Dong, C. Fu, M. Su, F. Jiang, D. Xu, R. Li, J. Qian, N. Wang, Y. Chen, and Q. Jiang, “Thyroid stimulating hormone (TSH) is associated with general and abdominal obesity: a cohort study in school-aged girls during puberty in east China,” Front. Endocrinol. (Lausanne)., vol. 30, no. 11, pp. 620, Sep. 2020.
[8] L. Pacifico, C. Anania, F. Ferraro, G. M. Andreoli, and C. Chiesa, “Thyroid function in childhood obesity and metabolic comorbidity,” Clinica Chimica Acta. Int. J. Clin. Chemistry., vol. 413 pp. 396–405, 2022.
[9] A. Habib, M. Molayemat, and Habib A, “Elevated serum TSH concentrations are associated with higher BMI Z-scores in southern Iranian children and adolescents,” Thyroid Res., vol. 13, no. 9, Jun. 2020.
[10] K. Walczak, and L. Sieminska, “Obesity and Thyroid Axis,” Int. J. Environ. Res. Public Health., vol. 7, no. 18(18), pp. 9434, Sept. 2021.
[11] J. He, Y. Lai, J. Yang, Y. Yao, Y. Li, W. Teng, and Z. Shan, “The relationship between thyroid function and metabolic syndrome and its components: a cross-sectional study in a chinese population,” Front. Endocrinol. (Lausanne)., vol. 31, no. 12, pp. 661160, Mar. 2021.
[12] I. Taranu, C. Lazea, V. Creț, N. Răcătăianu, M. Iancu, and S. D. Bolboacă, “Inflammation-related markers and thyroid function measures in pediatric patients: is the grade of obesity relevant?,” Diagnostics (Basel)., vol. 9, no. 11(3), pp. 485, Mar. 2021.
[13] X. Chen, S. Deng, C. Sena, C. Zhou, and V. V. Thaker, “Relationship of TSH levels with cardiometabolic risk factors in us youth and reference percentiles for thyroid function,” J. Clin. Endocrinol. Metab., vol. 8, no. 106(3), pp. e1221-e1230, Mar. 2021.
[14] P. Talwalkar, V. Deshmukh, and M. Bhole, “Prevalence of hypothyroidism in patients with type 2 diabetes mellitus and hypertension in India: a cross-sectional observational study,” Diabetes Metab. Syndr. Obes., vol. 12, pp. 369–376, 2019.
[15] T. I. Griadil, I. V. Chopey, K. I. Chubirko, and S. V. Feysa, “The clinical presentation of subclinical hypothyroidism in patients with type 2 diabetes mellitus associated with obesity, its impact on cardiovascular risk, and ways of its correction,” Wiad Lek., vol. 74, no. 10 cz 2, pp. 2634-2639, 2021.
[16] K. Singh, S. Devi, and P. K. Prabhakar, “Relationship of TSH with BMI in subclinical hypothyroid patients,” Biointerface Res. Appl. Chem., vol. 9, no. 4, pp. 4193-4198, 2019.
[17] M. Shilpashree, and B. Ravi, “Serum lipoprotein (a) and lipid profile in hypothyroidism,” J. Clin. Biomed. Sci., vol. 4, pp. 235-9, 2014.
[18] X. Ding, Y. Zhao, C. Y. Zhu, L. P. Wu, Y. Wang, Z. Y. Peng, C. Deji, F. Y. Zhao, and B. Y. Shi, “The association between subclinical hypothyroidism and metabolic syndrome: an update meta-analysis of observational studies,” Endocr. J., vol. 28, no. 68(9), pp. 1043-1056, Sep. 2021.
[19] M. Salerno, N. Improda, and D. Capalbo, “Management of endocrine disease Subclinical hypothyroidism in children,” Eur. J. Endocrinol., vol. 183(2), no.R13-R28, Aug. 2020.
[20] M. C. Vigone, D. Capalbo, G. Weber, and M. Salerno, “Mild hypothyroidism in childhood: who, when, and how should be treated?,” J. Endocr. Soc., vol. 25, no. 2(9), pp. 1024-1039, Jul. 2018.
[21] R. V. Jayakumar, “Clinical approach to thyroid disease,” J. Assoc. Physicians India., vol. 59, pp. 11-13, 2011.
[22] G. Gwinup, and M. E. Morton, “The high lying thyroid: a cause of pseudogoiter,” J. Clin. Endocr. Metab., vol. 40, pp. 37-42, 1975.
[23] U. Niranjan, and N. P. Wright, “Should we treat subclinical hypothyroidism in obese children?,” BMJ., vol. 352, pp. i941, 2016.
[24] World Health Organization (WHO). The WHO Child growth standards. June. 2016. Access: http://www.who.int/childgrowth/en/
[25] P. Zimmet, K. G. AlbertiG, F. Kaufman, N. Tajima, M. Silink, S. Arslanian, G. Wong, P. Bennet, J. Shaw, S. Caprio, and IDF consensus group, “The metabolic syndrome in children and adolescents-an IDF consensus report,” Pediatr. Diabetes, vol. 8, no. 5, pp. 299-306, 2007.
[26] L. Rodriguez, C. Dinauer, and G. Francis, “Treatment of hypothyroidism in infants, children and adolescents,” Trends Endocrinol. Metab., vol. 33, no. 7, pp. 522-532, Jul. 2022.
[27] M. C. Garin, A. M. Arnold, J. S. Lee, R. P. Tracy, and A. R. Cappola, “Subclinical hypothyroidism, weight change, and body composition in the elderly: the Cardiovascular Health Study,” J. Clin. Endocrinol. Metab., vol. 99, no. 4, pp. 1220-1226, Apr. 2014.
[28] B. Biondi, A. R. Cappola, and D. S. Cooper, “Subclinical hypothyroidism: a review,” JAMA., vol. 322, no. 2, pp. 153–160, 2019.
[29] G. Bona, F. Prodam, and A. Monzani, “Subclinical hypothyroidism in children: natural history and when to treat,” J. Clin. Res. Pediatr. Endocrinol., vol. 5 (Suppl 1), pp. 23-28, 2013.
[30] K. A. Metwalley, and H. S. Farghaly, “Subclinical hypothyroidism in children: updates for pediatricians,” Ann. Pediatr. Endocrinol. Metab., vol. 26, no.2, pp. 80-85, Jun. 2021.
[31] J.Y. Yao, P. Liu, W. Zhang, K. W. Wang, C. P. Lyu, Z. W. Zhang, X. L. Chen, Y. Chen, X. S. Wang, Y. X. Ding, L. J. Ma, J. Wang, and D. J. Sun, “Obesity rather than metabolic syndrome is a risk factor for subclinical hypothyroidism and thyroid autoimmunity,” Biomed. Environ. Sci., vol. 20, no. 34(10), pp. 819-823, Oct. 2021.
[32] T. Reinehr, “Thyroid function in the nutritionally obese child and adolescent,” Curr. Opin. Pediatr., vol. 23, no. 4, pp. 415-420, Aug. 2011.
[33] J. Francois, M. Al-Sadawi, J. Casillas, E. Botti, L. Soni, D. Ponse, S. M. Decamps, and S. I. McFarlane, “Hypothyroidism and heart failure: epidemiology, pathogenetic mechanisms & therapeutic rationale,” Int. J. Clin. Res. Trials., vol. 5, no. 1, pp. 146, 2020.
[34] V. Fatourechi, “Subclinical hypothyroidism: an update for primary care physicians,” Mayo Clin. Proc., vol. 84, no. 1, pp. 65-71, 2009.
[35] Y. Sun, D. Teng, L. Zhao, X. Shi, Y. Li, Z. Shan, and W. Teng, “Impaired sensitivity to thyroid hormones is associated with hyperuricemia, obesity, and cardiovascular disease risk in subjects with subclinical hypothyroidism,” Thyroid., vol. 32, no. 4, pp. 376-384, Apr. 2022.
[36] S. K. Y. Gosi, and V. V. Garla, “Subclinical hypothyroidism,” (Updated 2022 Jul 11). In: StatPearls (Internet). Treasure Island (FL): StatPearls Publishing; 2022 Jan–. Available from: https://www.ncbi.nlm.nih.gov/books/NBK536970/
[37] R. Sharma, “Nonalcoholic fatty liver disease and subclinical hypothyroidism in obese children,” Indian J. Pediatr., vol. 88, no. 5, pp. 425-426, May. 2021.
[38] G. S. Odabasi, E. A. Torel, and K. F. Nisanci, “The effect of subclinical hypothyroidism on body composition parameters in children,” Int. J. Clin. Pract., vol. 74, no. 9, pp. e13554, Sep. 2022.
[39] O. Kara, “Influence of subclinical hypothyroidism on metabolic parameters in obese children and adolescents,” Clin. Exp. Pediatr., vol. 63, no. 3, pp. 110-114, Mar. 2020.
[40] N. Akici, Z. E. Onal, T. Gürbüz, C. Sag, and S. Kilinç, “Atherogenic indices in the assessment of cardiovascular disease risk ıin children with obesity and subclinical hypothyroidism,” Acta. Endocrinol. (Buchar)., vol. 16, no. 3, pp. 334-338, Jul- Sep, 2020.
[41] M. Knez, and M. Glibetic, “Zinc as a biomarker of cardiovascular health,” Front. Nutr., vol. 8, pp. 686078, Jul. 2021.
[42] M. Donma, S. Kacmaz, A. Yilmaz, S. Guzel, and O. Donma, “The evaluation of new generation cardiovascular risk markers in childhood obesity,” Int. J. Med. Health Sci., vol. 15, no.12, pp. 308-314, 2021.